title: Resveratrol suppresses cell proliferation via inhibition of STAT3 phosphorylation and Mcl-1 and cIAP-2 expression in HTLV-1-infected T cells.
abstract: Adult T-cell leukemia (ATL) is an aggressive malignancy of peripheral T cells infected with human T-cell leukemia virus type 1 (HTLV-1). The prognosis of patients with aggressive ATL remains poor because ATL cells acquire resistance to conventional cytotoxic agents. Therefore, development of novel agents is urgently needed. We examined the effects of resveratrol, a well-known polyphenolic compound, on cell proliferation and survival of HTLV-1-infected T-cell lines, MT-2 and HUT-102. We found that resveratrol suppressed cell proliferation and induced cell death of MT-2 and HUT-102 cells. Immunoblot analysis showed inhibition of myeloid cell leukemia sequence (Mcl)-1 and cellular inhibitor of apoptosis protein (cIAP)-2 expression as well as signal transducers and activators of transcription (STAT) 3 phosphorylation at Tyr(705) and Ser(727) in resveratrol-treated cells. We also observed cleavage of caspase-3 and poly(ADP-ribose) polymerase in resveratrol-treated cells, indicating that resveratrol induces caspase-dependent apoptosis in MT-2 and HUT-102 cells. In addition, the STAT3 inhibitor S3I-201 not only induced cell growth arrest and cell death but also activated caspase-3 in MT-2 and HUT-102 cells, indicating that STAT3 may be a therapeutic target for ATL. These results suggest that resveratrol presents a potent anti-proliferative effect in part via the suppression of STAT3 phosphorylation and Mcl-1 and cIAP-2 expression in HTLV-1-infected T cells. Resveratrol merits further investigation as a potential chemotherapeutic agent for ATL.
authors.affiliation: Hematology & Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Iwate 020-8505, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ito
authors.forename: Ryousei
authors.initials: R
authors.lastname: Sasaki
authors.forename: Maki
authors.initials: M
authors.lastname: Asahi
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ishida
mesh_terms: D016587:Antimutagenic Agents / Q000494:pharmacology*; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D015490:HTLV-I Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology / Q000821:virology; D044767:Ubiquitin-Protein Ligases
chemical_list: D016587:Antimutagenic Agents; D051034:Inhibitor of Apoptosis Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013267:Stilbenes; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; D000077185:Resveratrol
keywords: Adult T-cell leukemia; Mcl-1; Resveratrol; STAT3; cIAP-2